Need for better diastolic stress test: twistin’ time is here?

This editorial refers to ‘Dynamic change in left ventricular apical back rotation: a marker of diastolic suction with exercise’, by S.-J. Hong et al., pp. 12–19. The left ventricle (LV) has two alternating phases, systolic contraction and diastolic filling with isovolumic relaxation as transition phase with decrease in active fibre stress, ultimately bringing LV pressure below left atrial (LA) pressure, thereby initiating LV filling. In addition to myocardial relaxation, release of restoring forces contribute to the fall in LV pressure during isovolumic relaxation. Restoring forces are generated in systole when the ventricle contracts below its unstressed volume and are released in early diastole when the ventricle relaxes. This is analogous to manual compression of an elastic spring which recoils back to its resting length when compression is released (Figure 1). Since restoring forces are generated in systole, their magnitude is determined by systolic function. Schematic illustration of mechanisms and echocardiographic parameters of LV early-diastolic function. Based on Opdahl et al.1,2 Relaxation and restoring forces exert their effect simultaneously and there is no clinical method to differentiate between contributions from each of the mechanisms. In invasive studies when using high fidelity pressure catheter, the combined effect of relaxation and restoring forces can be assessed as decay rate of LV pressure measured as time constant of LV isovolumic pressure fall (tau).3 Left ventricular early diastolic function is also reflected in the level of minimum diastolic pressure. Impairment of early diastolic function when due to slowing of relaxation, loss of restoring forces or both, result in elevation of minimum early diastolic pressure. In normal hearts myocardial relaxation and restoring forces bring minimum LV pressure close to zero. Furthermore, vigorous restoring forces can generate negative minimum LV pressures. Since ventricular filling starts prior to minimum LV pressure, negative pressure is often not observed. The interaction between LV end-systolic volume, restoring forces, and diastolic filling illustrates the tight coupling between systolic and diastolic function. As illustrated in Figure 1, LV early-diastolic function can be evaluated clinically by tissue Doppler echocardiography to measure mitral annulus velocity (e′), which in principle represents LV lengthening velocity, and speckle tracking echocardiography to measure LV untwisting velocity.4 As shown previously, both e′ and untwisting velocity reflect relaxation and restoring forces.1,2 As suggested by experimental studies,5 loss of diastolic suction is an important contributor to exercise induced elevation of LA pressure. These experiments showed that a normal heart can increase transmitral flow during exercise with little or no increase in LA pressure by lowering minimum LV diastolic pressure (Figure 2). In the failing heart, however, there was no fall in minimum LV diastolic pressure with exercise and increase in transmitral gradient and mitral flow was achieved by elevation of LA pressure. Possibly, a similar mechanism explains elevated LA pressure during exercise in patients with heart failure. In a study which used infusion of cathecholamines to simulate exercise in patients with apparently intact LV function, LV minimum pressure became negative,6 suggesting that a similar mechanism may be operative in the normal human heart. Exercise induced change in LA pressure: Experimental study showing a normal heart (left panel) which generates increasingly negative LV early-diastolic pressure (PLV) during exercise. Thereby, the normal heart can increase mitral flow with no rise in LA pressure (PLA). During heart failure (right panel), there is no fall in LV diastolic pressure with exercise and transmitral flow increases by elevation of LA pressure. E, early diastolic transmitral flow rate measured as dV/dt.5 As shown by Remme et al.,7 negative early diastolic pressures implies that the LV wall performs work to pull blood into the ventricle. Therefore, LV filling with negative LV pressure implies diastolic suction. There is, however, an alternative definition of suction which is ventricular filling during falling pressure,8 and suction according to this definition does not include negative LV pressure or release of restoring forces. Both definitions are proven useful and in studies of LA filling using wave intensity analysis, definition of suction as filling during falling pressure was helpful in understanding atrial filling mechanics.9 In the present issue of the journal, Hong et al.10 investigate effect of exercise on LV early diastolic function using high-fidelity LV pressure catheters in combination with echocardiography to measure e′ and untwisting velocity. In patients with normal left ventricular ejection fraction (LVEF), previously treated for coronary artery disease, they showed a range of responses when measuring minimum LV diastolic pressure, tau, and untwisting velocity. They grouped patients into those with and without exercise induced decrease in minimum LV diastolic pressure, respectively. Patients with decrease in minimum LV diastolic pressure had most marked increase in LV untwisting velocity with exercise. Furthermore, e′ velocity during exercise was highest in patients with decrease in minimum LV diastolic pressure. Change in LV end-systolic volume was similar in patients with decrease and increase in LV minimum pressure, suggesting that restoring forces was not accounting for the difference in e′ and untwisting velocity. The time constant of LV pressure decay decreased markedly with exercise in patients with lowering of minimum diastolic pressure, but was unchanged in the group with elevation of minimum LV pressure. This suggests that impaired LV relaxation explained lower untwisting velocity and attenuated e′ response in the group with elevated minimum LV diastolic pressure with exercise. The diastolic stress test was introduced by Ha et al.11 and includes measuring E/e′ and tricuspid regurgitation velocity prior to and during exercise. The test is not widely used, in part reflecting technical challenges.12 A non-invasive diastolic stress test is needed, however, since patients with heart failure and normal LVEF may have normal filling pressures at rest, and therefore exercise may be needed to make the diagnosis as shown recently by Obokata et al.13 As suggested by the study of Hong et al.10 untwisting velocity may help to identify patients with severely impaired diastolic function during exercise. This was, however, a small study and is essentially a demonstration of a mechanistic principle. A larger non-invasive study or a study with right heart catheterization and pulmonary capillary wedge pressure as estimate of LA mean pressure is needed to investigate the feasibility and added diagnostic value of measuring untwisting velocity. Hong et al.10 used LV apical rotation as an index of twist, and as shown previously this is a valid approximation since apical rotation represents the dominant contribution to LV twist.14 More work is needed to refine and standardize the methodology for measuring twisting deformation, but provided the technique is improved, untwisting velocity may become an important addition to the diastolic stress test. Developments within 3D speckle tracking echocardiography are likely to improve accuracy and reproducibility of twist quantification. Conflict of interest: None declared.